Aetna considers cholesterol skin testing experimental and investigational because its effectiveness in predicting coronary heart disease risk as compared to standard methods of cholesterol testing has not been established.

Aetna considers breath isoprene measurements for screening members for lipid disorders or monitoring of the success of therapies in persons with lipid disorders experimental and investigational because its effectiveness has not been established.

Levels of serum cholesterol have been correlated with a person's subsequent risk of heart disease. Clinical studies have shown that serum cholesterol screening may reduce the risk of heart disease in adults, and for high-risk children and adolescents.

The U.S. Preventive Services Task Force (USPSTF) recommends periodic total serum cholesterol and high-density lipoprotein cholesterol (HDL-C) screening for all men aged 35 and older. The USPSTF recommends screening beginning at aged 20 for both men and women with other risk factors for coronary heart disease (e.g., diabetes, family history suggestive of hyperlipidemia, a family history of cardiovascular disease before age 50 years in male relatives or age 60 years in female relatives, or patients with multiple coronary heart disease risk factors (e.g., tobacco use, hypertension)). They concluded that an interval of 5 years has been recommended, but longer intervals may be reasonable in low-risk subjects, including those with previously desirable cholesterol levels. For average risk individuals, the benefit of measuring triglycerides as an initial screening is unproven.

The USPSTF recommends screening with total cholesterol, HDL-C, and lipoprotein analysis for persons with major coronary heart disease risk factors (e.g., smoking, hypertension, and diabetes). These guidelines recommend, for high-risk persons, lipoprotein analysis to help identify individuals at highest risk of coronary heart disease (CHD) in whom individual diet or drug therapy may be indicated. The optimal frequency of screening has not been determined and is left to clinical discretion.

In a statement on screening for lipid disorders in children, the USPSTF (2007) concluded that the evidence is insufficient to recommend for or against routine screening for lipid disorders in infants, children, adolescents, or young adults (up to age 20).

The American College of Physicians (ACP) - American Society of Internal Medicine, in guidelines revised in 1996, concluded that screening serum cholesterol was appropriate but not mandatory for asymptomatic men aged 35 to 65 and women aged 45 to 65; the guidelines do not recommend screening for younger persons unless they have evidence of having a familial lipoprotein disorder or have multiple cardiac risk factors. The ACP concluded that evidence was not sufficient to recommend for or against screening asymptomatic persons between the ages of 65 and 75, but the ACP recommends against screening after age 75.

The Canadian Task Force on the Periodic Health Examination concluded there was insufficient evidence to recommend routine cholesterol screening but endorsed case-finding in men 30 to 59 years old.

Also, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III, convened by the National Heart and Blood Institute, recommends routine measurement of a fasting lipoprotein profile (total cholesterol, LDL cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride) in all adults age 20 and older at least once every 5 years. The American Academy of Family Physicians recommends measurement of total cholesterol at least every 5 years in adults age 19 and older.

The American College of Obstetricians and Gynecologists recommends periodic screening of cholesterol in all women over age 20, and in selected high-risk adolescents.

Selective screening of children and adolescents is recommended by the NCEP Expert Panel on Blood Cholesterol Levels in Children and Adolescents, the National Center for Education in Maternal and Child Health's Bright Futures guidelines, the American Medical Association Guidelines for Adolescent and Preventive Services (GAPS), and the American Academy of Family Physicians. Screening with non-fasting cholesterol in all children and adolescents who have a parental history of hypercholesterolemia, and with fasting lipid profile in those with a family history of premature cardiovascular disease, is recommended by these organizations. These organizations also recommend that children who have multiple risk factors for CHD (such as smoking or obesity) and whose family history can not be ascertained be screened at the discretion of the physician.

An updated report on lipid screening in childhood by the American Academy of Pediatrics (Daniels et al, 2008) stated that a fasting lipid profile is recommended after 2 years of age for children and adolescents with a family history of dyslipidemia or premature (less than or equal to 55 years of age for men and less than or equal to 65 years of age for women) cardiovascular disease or dyslipidemia, and in children for whom family history is not known or those with other cardiovascular disease risk factors, such as over-weight (body mass index [BMI] greater than or equal to 85th percentile but less than 95th percentile), obesity (BMI greater than or equal to 95th percentile), hypertension (blood pressure greater than or equal to 95th percentile), cigarette smoking, or diabetes mellitus. If the values are normal on initial screening, re-testing is recommended in 3 to 5 years. The AAP does not recommend screening before 2 years of age.

The NCEP recommends screening once with total blood cholesterol for children and adolescents 2 years of age or older whose parents have a blood cholesterol level greater than 240 mg/dL. The NCEP recommends periodic total blood cholesterol screening children and adolescent with several risk factors whose family history can not be ascertained; the optimal screening frequency for high blood cholesterol in this risk group has not been determined and is left to clinical discretion. Risk factors for coronary vascular disease include smoking, hypertension, physical inactivity, obesity, and diabetes mellitus. The NCEP recommends screening once with a fasting lipid profile for children and adolescents 2 years of age and older with a family history of coronary or peripheral vascular disease before the age of 55 years. Although routine cholesterol screening is recommended only for high-risk children, pediatricians should suggest that all children 2 years of age and older follow the American Heart Association's Step One Diet, which is essentially a low-cholesterol diet.

The NCEP recommends measurement of triglyceride levels. According to the NCEP, calculated very low density lipoprotein (VLDL) levels are sufficiently accurate; VLDL is calculated as total triglycerides divided by 5. The NCEP recommends direct measurement of LDL cholesterol in persons with triglyceride levels greater than 400 mg/dL, as calculated LDL cholesterol measurements may be inaccurate at that level of hypertriglyceridemia. Directly measured LDL cholesterol is not recommended for persons without hypertriglyceridemia because calculated LDL cholesterol levels are sufficiently accurate.

Cholesterol skin testing is a non-invasive test that entails placement of a few drops of fluid in the fleshy area of the palm near the base of the thumb and measurement of the resulting color change with a special device. The new test, known as Cholesterol 1,2,3TM (IMI International Medical Innovations Inc., Toronto, Canada), does not involve fasting or waiting hours or days for results, which will be available in 3 minus. Well-designed clinical trials are needed to ascertain the effectiveness of cholesterol skin testing in predicting CHD as compared to standard methods of cholesterol testing (e.g., blood cholesterol tests).

Reiter and colleagues (2007) evaluated the role of skin tissue cholesterol (SkinTc) in predicting the presence of atherosclerosis. SkinTc concentrations were determined in 318 consecutive patients by using the non-invasive PREVU POC Skin Sterol Test. Additionally, a complete lipid status and cardiovascular risk profile according to the PROCAM and Framingham scores as well as an evaluation by carotid duplex sonography and ankle-brachial blood pressure index testing was obtained from all patients. SkinTc concentrations did not differ significantly among patients suffering from cerebrovascular disease (CVD) and peripheral arterial disease (PAD) compared to the corresponding control groups and among patients with a calculated cardiovascular risk greater than 10 % in 10 years compared to patients with a risk less than 10 % (all p > 0.05). Additionally, SkinTc concentrations were not significantly higher in the 245 patients with at least one documented atherosclerotic disease compared with the remaining 73 patients without evidence of atherosclerosis. The authros concluded that SkinTc concentrations determined by the PREVU POC Skin SterolTest are not related to the presence of CVD and PAD or to an elevated cardiovascular risk, indicating that this parameter can not be used as a reliable indicator of atherosclerosis.

Isoprene is a volatile compound that is formed endogenously in humans. While the biochemical pathways of biosynthesis and exact origins of isoprene found in human breath are still unclear, its measurement in exhaled breath has been suggested as a non-invasive indicator with diagnostic potential. It has been suggested that isoprene is related to cholesterol biosynthesis. As a result, breath isoprene measurements could potentially be used for mass screening for lipid disorders and may serve as an additional parameter to complement invasive tests for monitoring the effectiveness of lipid-lowering therapy (pharmacological agents and/or dietary or lifestyle modifications). However, this test has not yet reached the level of routine clinical methods and is still under development (Salerno-Kennedy and Cashman, 2005). In a review on the diagnostic potential of breath analysis of volatile organic compounds, Miekisch and colleagues (2004) noted that due to technical problems of sampling and analysis and a lack of normalization and standardization, huge variations exist between results of different studies. The authors stated that these are among the main reasons why breath analysis could not yet been introduced into clinical practice.

O'Hara et al (2008) stated that analysis of volatile organic compounds (VOCs) on human breath has great potential as a non-invasive diagnostic technique. It is, thus, surprising that no single, standard procedure has evolved for breath sampling. These researchers presented a novel repeated-cycle isothermal re-breathing method, where 1 cycle comprises 5 rebreaths, which could be adopted for breath analysis of VOCs. For demonstration purposes, the authors presented measurements of 3 common breath VOCs: (i) isoprene, (ii) acetone and (iii) methanol. Their concentrations measured in breath are shown to increase with number of re-breaths until a plateau value is reached by at least 20 re-breaths. The average ratio of plateau concentration to single mixed expired breath concentration was found to be 1.92 +/- 0.57 for isoprene, 1.25 +/- 0.13 for acetone and 1.12 +/- 0.12 for methanol. Measurements from on-line single exhalations were presented, which demonstrated a positive slope in the time-dependent expirograms of isoprene and acetone. The slope of the isoprene expirogram was persistently linear and the end-expired concentration of isoprene was highly variable in the same subject depending on the duration of exhalation. End-expired values of acetone are not as sensitive to the length of exhalation, and were the same to within measurement uncertainty for any duration of exhalation for any subject. The authors concluded that uncontrolled single on-line exhalations are unsuitable for the reliable measurement of isoprene in the breath and that re-breathing can be the basis of an easily tolerated protocol for the reliable collection of breath samples.

Tashakkor and Mancini (2013) provided a systematic review of clinical data to assist physicians counselling patients that have undergone skin cholesterol testing and provided a framework for future research. Multiple electronic databases were systematically searched for studies published from 1970 through February 2013. Selection criteria included English language, peer-reviewed studies that quantitatively examined the relationship between non-invasively measured skin cholesterol levels and indices of vascular disease or cardiovascular risk factors in human subjects. These researchers identified 9 cohorts reported in 11 studies. The studies suggested that skin cholesterol does not correlate with traditional markers of cardiovascular disease such as serum lipid values and inflammatory markers, and integrated risk scores (Framingham and Prospective Cardiovascular Munster [PROCAM]). Single studies reported a significant relationship between skin cholesterol levels and evidence of underlying atherosclerosis as implied by positive exercise testing, invasive coronary angiography, increased calcium scores in Caucasian patients, and presence of carotid plaque detected using B-mode ultrasound. Two studies identified a significant relationship using B-mode measurements of carotid intima medial thickening. The authors concluded that skin cholesterol might be a marker of underlying vascular atherosclerosis. Moreover, they stated that further prospective investigations are needed to establish utility of this point-of-care test for identifying subjects warranting formal cardiovascular risk assessment.

CPT Codes / HCPCS Codes / ICD-9 Codes

CPT codes covered if selection criteria are met:

80061

82465

83718

84478

CPT codes not covered for indications listed in the CPB:

83719

ICD-9 codes covered if selection criteria are met:

V77.91

Screening for lipoid disorders

Other ICD-9 codes related to the CPB:

249.00 - 249.91

Secondary diabetes mellitus

250.00 - 250.93

Diabetes mellitus

272.0 - 272.9

Disorders of lipoid metabolism

278.00 - 278.01

Obesity

305.1

Tobacco use disorder

401.0 - 405.99

Hypertensive disease

414.00 - 414.9

Other forms of chronic ischemic heart disease

429.9

Heart disease, unspecified

440.0 - 440.9

Atherosclerosis

444.0 - 444.9

Arterial embolism and thrombosis

V17.3

Family history of ischemic heart disease

V17.41 - V17.49

Family history of other cardiovascular diseases

V18.0

Family history of diabetes mellitus

V18.11 - V18.19

Family history of other endocrine and metabolic diseases

Hypertriglyceridemia:

CPT codes covered if selection criteria are met::

83721

Lipoprotein, direct measurement; LDL cholesterol

ICD-9 codes covered if selection criteria are met::

272.1

Pure hyperglyceridemia

272.2

Mixed hyperlipidemia

The above policy is based on the following references:

American Academy of Family Physicians (AAFP). Summary of policy recommendations for periodic health examinations. Leawood, KS: AAFP; August 2003.

American Academy of Pediatrics, Committee on Nutrition. Statement on cholesterol. Pediatrics. 1992;90(3):469-473.

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.

Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.